Discovery and investigation of therapeutically important marine natural products

For many years Harbor Branch Oceanographic Institute operated the Johnson-Sea-Link human occupied submersible allowing for the collection of organisms from depths up to 3000 feet of seawater. Use of the submersible coupled to more standard collection methods such as scuba and snorkeling has led to a collection of over 18,000 marine macro organisms and 19,000 microbial isolates that are used in our research. As part of an NIH funded National Cooperative Drug Discovery Group, we began creating an “enriched peak library” to overcome the issues related to screening crude extracts and the need for extensive bioassay-guided fractionation. With funding from NCCAM we greatly expanded our enriched fraction library. The library has been created using a Combiflash™ Companion™ Flash Chromatography System which separates crude extracts into highly enriched fractions, many of which can be up to 90% of a single component. Screening of the library has allowed us to find new modulators of gamma secretase; inhibitors of NFκB; compounds that modulate mast cell function related pancreatic cancer; antiplasmodial compounds and compounds selectively active against the intra-macrophage form of TB, to name a few activities. The presentation will highlight the use of the peak library in discovery of active natural products as well as some of our recent findings related to applications of natural products to cancer drug development.